Abstract
BACKGROUND AND AIMS: Genetic testing is recommended for select patients with atrial fibrillation (AF). The aims of this study were to define the results of genetic evaluation and its therapeutic impact for patients referred to a dedicated AF precision medicine clinic. METHODS: Patients diagnosed with AF before age 60 were candidates for referral. In addition to standard evaluation with history, physical exam, and ECG, genetic evaluation included a 3-generation pedigree, cardiac imaging, ambulatory monitoring, and clinical genetic testing with a cardiomyopathy/arrhythmia panel. RESULTS: 264 participants were referred: the median age was 47 years (Q1, Q3: 38, 55), 77 (29%) were female, and 236 (89%) were White. Median age at AF diagnosis was 39 years (Q1, Q3: 31, 48) and median time from AF diagnosis to evaluation was 3.7 years (Q1, Q3: 0.9, 10). 242 patients (92%) underwent genetic testing, which identified a pathogenic or likely pathogenic variant in 48 (20%). The strongest predictors of positive genetic testing were history of cardiomyopathy, infranodal conduction disease, and elevated T1 or late gadolinium enhancement on cardiac MRI (all p<0.05). The strongest predictors of negative genetic testing were obstructive sleep apnea and a normal 12-lead ECG (both p<0.04). Overall, genetic testing changed clinical management in 52% of patients with positive genetic testing, highlighted by 7 new ICD placements and initiation of disease modifying therapy in 16 patients. CONCLUSIONS: Genetic testing was positive in 20% of patients with early-onset AF referred to a dedicated AF precision medicine clinic. Genetic testing results changed clinical management in approximately half of genotype-positive patients. STRUCTURED GRAPHICAL ABSTRACT: Key Question: Does genetic evaluation of patients with early-onset atrial fibrillation (AF) change their clinical management?Key Finding: Among 246 participants that completed genetic evaluation in a dedicated AF precision medicine clinic, 20% had positive genetic testing with identification of a pathogenic cardiomyopathy or channelopathy variant. These findings led to changes in clinical management in 52% of patients with positive genetic testing.Take-home Message: Genetic evaluation of patients with early-onset AF consists of detailed phenotyping and genetic testing to identify previously undiagnosed genetic disorders. This facilitates earlier diagnosis and clinical intervention.